Pyrimidotriazinone compounds

ABSTRACT

Substituted 1H,4H-pyrimido( 2,1-c)-(1,2,4)triazin-6-ones are prepared by reacting an appropriately substituted thiazolo- or oxazolo-(3,2-a)pyrimidin-5-one with a hydrazino compound. The resultant pyrimidotriazinones possess anti-fungal and anthelmintic activity.

United States Patent [151 3,694,441 Dunwell et al. [45] Sept. 26, 1972[54] PYRIMIDOTRIAZINONE COMPOUNDS [56] References Cited [72] Inventors:David Wllllam Dunwell, 27 Alexan- UNITED STATES PATENTS a A camberley,y; Delme 3,213,090 10/1965 Roch ..260/249.S x Evans, Springwoods,Sandhurst, Berkshire, both of England Primary Examiner-John M. Ford 5,Attorney-Everet F. and Walter E- Buting [21] Appl. No.: 121,597 [57]ABSTRACT Substituted lH,4l-l-pyrirnido[ 2, 1-c]-[ l,2,4]triazin-6 52 US.Cl ..260/249.5, 424/249 ones are p p y reacting an pp p y 51 1111.0...C07d 57/12 Sfiwted thiazoloor OXaZOIO-I3l-alpyrimidifl-5-one 58 Fieldof Search ..260/249.5 with a hydrazim The resultant pyrimidotriazinonespossess anti-fungal and anthelmintic activity.

10 Claims, No Drawings Nk mfg/L613;

wherein R represents hydrogen, C alkyl or -CH Ar in which Arrepresentsphenyl optionally substituted by halogen, nitro, C alkylor C alkoxy; Rrepresents hydrogen, C, alkyl or the group Ar as defined above, the twoR groups being the same or different; R is hydrogen'or C alkyl; and Rrepresents hydrogen or --COR in which R is C alkoxy, C, alkylamino, or-NHN(R) where R is as defined above and the two R groups may be the sameor different.

By the term C alkyl as used herein, we mean saturated aliphatichydrocarbon groups having from one to five carbon atoms, exemplary: ofwhich are methyl, ethyl, n.propyl, isopropyl, n.butyl, s.butyl, t.butyl,n.amyl ands.arnyl.- The tenn C alkoxy" means the aforementioned C alkylgroups linked through an oxygen atom such as methoxy, ethoxy,isopropoxy, n.butoxy, s.butoxy and m.amyloxy. The term C alkylaminomeans an amino group, one or two of the hydrogenatoms of which arereplaced by C alkyl, such as methylamino, dimethylamino, ethylamino,din.propylamino, isopropylamino, t.butylamino and mamylamino.

A preferred group of compoundsfalling within the scope of compounds offormula I are those where R represents hydrogen, C, alkyl, benzyl,halobenzyl or nitrobenzyl; one of R is hydrogen and the other R ishydrogen, methyl, ethyl, phenyl, halophenyl or nitrophenyl; R ishydrogen, methyl or ethyl; and R is hydrogen, methoxycarbonyl,'ethoxycarbonyl propoxycarbonyl, butoxycarbonyl, methylaminocarbonyl,dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl,hydrazinocarbonyl, methylhydrazinocarbonyl, dimethylhydrazinocarbonyl,ethylhydrazinocarbonyl, diethylhydrazinocarbonyl orbenzylhydrazinocarbonyl.

The compounds of formula I may be prepared by a method which comprisesreacting an appropriately sub stituted thiazolooroxazolo-[3,2-a1-pyrimidin-5-one of formula:

RLIE4N 5 4 2 VI R 1 8 R with a hydrazino compound of the formula:

l-l NNl-lR Ill wherein R, R, R and R are as defined above and X isoxygen or sulphur, the reaction being carried out in a suitable reactionsolvent, for example ethanol, and normally at reflux for periods of from0.5 up to 125 hours depending on the reactants being used. Normally theoxazolo compounds of formula II react more rapidly than thecorresponding thiazolo compounds. To avoid obtaining a mixture ofproducts of formula I, the compound of formula III is preferablyhydrazine itself or hydrazine hydrate and the resultant compound offormula l in which R is hydrogen is subsequently alkylated or benzylatedin conventional manner, for example using silver oxide and anappropriate alkyl or benzyl halide, to produce the desired compound inwhich R is (3 .5 01' CHQAI'.

When R in formula lI is an alkoxycarbonyl group andan excess ofhydrazine is used in the reaction, the resultant product of formula I isa carboxylic acid hydrazide, i.e., the alkoxycarbonyl group of thestarting material is replaced by a hydrazinocarbonyl groupsimultaneously with the ringexpansion. A carboxylic acid hydrazide canalso, of course, be prepared by refluxing a resultant compound offormula I in which R is alkoxycarbonyl with a further quantity of thecompound of formula III. Similarly a compound of formula I in which R isalkoxycarbonyl can readily be converted to the corresponding compound inwhich R is alkylaminocarbonyl by reaction with the appropriatealkylamine.

Specific compounds which can be prepared by the process of thepresentinvention include: 3-r nethylll-l,4l-l-pyrimido[2, 1-c]-[ 1,2,4]triazin-6-one 8-methylll-l,4H-pyrimido[2, 1-c]-[ l ,2,4]triazin-6-one3,4-diethyl-1H,4H-pyrimido[2,l-c]-[ l ,2,4 ltriazin-6- one4,8-dimethyl-1H,4l-l-pyrimido[2,l-c]-[ l ,2,4]triazin-6- one one 1-s.butyl-7-ethoxycarbonyll H,4H-pyrimido[ 2, l-c]-[ l ,2,4]triazin-6-one1 --methyl- 7-ethoxycarbonyll H,4l-l-pyrimido[ 2, l-c l,2,4]triazin-6-one l-methyl-7-t.butoxycarbonyll H,4l-I-pyrimido[ 2, l -cH l ,2,4]triazin-6-one 3-methyl-7-ethoxycarbonyll H,4H-pyrimido[ 2, l -cl ,2,4]triazin-6-one l ,3-dimethyl-7-ethoxycarbonyll l-I,4H-pyrimido[2,l c]-[ l,2,4]triazin-6-one l-benzyl-7-ethoxycarbonyl-1H,4H-pyrimido[2,l-c]-[ l ,2,4]triazin-6-onel-p.nitr0benzyl-7-ethoxycarbonyllH,4H-pyrimido[ 2, l -c]-[l,2,4]triazin-6-one l-o-chlorobenzyl-7-t.butoxycarbonyll H,4H- pyrimido[2, l -c]-[ l ,2,4]triazin-6-one l -p.methylbenzyll H,4l-l-pyrimido[2, l-c H l ,2,4] triazin-6-one l-p.methoxybenzyll H,4H-pyrimido[ 2, l -c]-[l ,2,4] triazin-6-one 3-phenyl-7-ethoxycarbonyll H,4l-l-pyrimido[ 2, l-c] 1 ,2,4]triazin- 6-one 3-p.nitrophenyl-7-ethoxycarbonylll-l,4H-pyrimido[ 2,1-c]-[ l,2,4]triazin-6-one 3-phenyl-7-ethoxycarbonyl-8-methyll H,4H-pyrimido [2,l-c]-[ l ,2,4]triazin-6-one7-ethoxycarbonyll H,4l-l-pyrimido[ 2, 1-c]-[ l ,2,4] triazin-6-0ne N',N'-dimethyll l-l,4l-l-pyrimido[ 2, l -c]-[ l ,2,4]triazin- 6-one,7-carboxarnide N-propyll H,4H-pyrimido[2, l -c]-[ l ,2,4]triazin-6- one,7-carboxamide l,N'-dimethyll I-I,4I-I-pyrimido[2, l -c]-[ l,2,4]triazin-6-one, 7 carboxamide N'-methyl-3-o.tolyl- 1 I-I,4I-I-pyrimido[ 2, l c]-[1,2,4]triazin6-one, 7 carboxamide N'-ethyll -benzyl-4,8-dimethyllI-I,4I-I-pyrimido[ 2, l c]-[ l,2,4]triazin-6-one, 7-carboxamide 1H,4H-pyrimido[2, l -c]-[ 1,2,4]triazin-6-one, 7-carboxylic acid hydrazide1,3,N'-trimethyll H,4H-pyrimido[2, l-c]-[ l,2,4]triazin-6-one,7-carboxylic acid hydrazide l-s.butyll I-I,4I-I-pyrimido[2, l -c]-[l,2,4]triazin-6-one, 7-carboxylic acid hydrazide 3-methyllI-I,4H-pyrimido[2, l -c]-[ l,2,4]triazin-6-one, 7-carboxylic acidhydrazide l-p.nitrobenzyl-1I-I,4I-I-pyrimido[2, l-c]-[ l,2,4]triazin-6-one, 7-carboxylic acid hydrazide4,8-diphenyl-lI-I,4I-I-pyrimido[2,l-c]-[ l ,2,4]triazin-6- one,7-carboxylic acid hydrazide l-isopropyll I-I,4l-I-pyrimido[ 2, l -c]-[ l,2,4]triazin-6 one, 7-carboxylic acid hydrazide l,N'-dibenzyl- 1H,4I-I-pyrimido[2, l -c]-[ l ,2,4]triazin- 6-one, 7-carboxylic acidhydrazide N'-methyl-3-phenyll H,4I-I-pyrimido[2, l -c]-[1,2,4]triazin-6-one, 7-carboxylic acid hydrazide l-n.amyllI-I,4I-I-pyrimido[ 2, l-c]-[ l,2,4]triazin-6-one, 7-carboxylic acidhydrazide N-t.butyll H,4l-I-pyrimido[2, l -c]-[ l,2,4]triazin-6- one,7-carboxylic acid hydrazide l-p.chlorobenzyll H,4H-pyrimido[ 2, l c]-[1,2,4] triazin-6-one, 7-carboxylic acid hydrazide The intermediatecompounds of formula II used in the process of the present invention areeither known or are prepared by known methods, for example as describedin the Journal of Organic Chemistry, 1959, 24, 779, The followingExamples illustrate the general process used for preparing oxazolo-andthiazolointermediates of formula II.

EXAMPLE A A solution of 2-aminooxazole (l0.8 g.) was heated under refluxfor 2 hours with diethyl ethoxymethylene malonate (27.5 g.) in1,2,4-trichlorobenzene (100 ml. The ethanol which formed in the reactionwas collected, the remaining solution allowed to cool and the solidwhich formed was filtered off, washed in ether and dissolved inisopropanol. After treatment with carbon, the solution was allowed tocool and the crystals formed were filtered ofi to give6-ethoxycarbonyl-5-oxazolo[ 3,2-a]pyrimidinone, m.p. l30- 133 C. (dec.).

EXAMPLE B Using the method of Example A but with 2-amino-5-phenylthiazole and diethyl ethoxymethylene malonate,6-ethoxycarbonyl-2phenyl-5-thiazolo-[3,2-a] pyrimidinone was obtained,m.p. 189 C. from chloroform/carbon tetrachloride.

As stated previously, the compounds of formula I possess anthelminticactivity and are especially effective against Nematospiraides dubius andSyphacia bvelata. Dosage levels vary depending upon the compound beingused, the animal to be treated, and the helminth to be controlled but,in general, the compounds of the present invention are administered in asingle dose of from 50 to 300 mg./Kg. of animal body weight.

The compounds of the invention may be administered in a variety of waysbut normally as a single oral or parenteral dose at a time whenhelminthiasis is apparent or suspected. The dose administered may, ofcourse, contain other anthelmintics, parasiticides or antibacterials.

In general, compositions containing the active anthelmintic compound areused; the amounts of the anthelmintic ingredient in the composition, aswell as the remaining constituents, will vary according to the type oftreatment, the host animal, and the particular parasitic disease. Ingeneral, however, compositions containing a total weight percent of theactive compound or compounds ranging from 0.001 to 95% will be suitablewith the remainder being any suitable carrier or vehicle.

A number of modes of treatment may be used, and each to some extentdetermines the general nature of the compositions. For example, theanthelmintic compounds may be administered to domesticated animals in asingle unit oral dosage form such as a tablet, bolus, capsule or drench,or in the liquid oil base fonn suitable for parenteral administration;or they may be compounded as a feed premix to be later admixed with theanimals food.

When the compositions are to be solid unit dosage forms, such as intablets, capsules, or boluses, the ingredients other than the activecompounds may be any other pharmaceutically acceptable vehiclesconvenient in the preparation of such forms, and preferably materialsnutritionally suitable, such as starch, lactose, talc, magnesiumstearate and vegetable gums. In capsules, the active compound may beused in essentially undiluted form, the only extraneous material beingthat of the capsule casing itself, which may be hard or soft gelatin orany other pharmaceutically acceptable encapsulating material. When thedosage fonn is a liquid oil base form, the active compound is suitablyadmixed with an acceptable oil base vehicle, preferably of the vegetableoil variety, such as peanut oil or cotton-seed oil. In all of suchforms, i.e., in tablets, boluses, capsules, and oil base formulations,the active compound conveniently ranges from about 5 to by weight of thetotal composition.

When the unit dosage form is to be in the form of a drench, theanthelmintic agents may be mixed with agents which will aid in thesubsequent suspending of the active compound in water, such asbentonite, clays, water-soluble starches, cellulose derivatives, gumsand surface active agents, to form a dry pre-drench composition, whichis added to water just before use. In the pre-drench formulation, inaddition to the suspending agent, such ingredients as preservatives andanti-foam compounds may be included. Such a dry product may contain asmuch as by weight of the active compound, the rest being contributed bythe excipients. Preferably, the solid composition contains from 30 to95% by weight of the active compound. Enough water should be added tothe solid product to provide the proper dosage level within a convenientamount of liquid for a single oral dose. Liquid drench formulationscontaining from about 10 to 30 weight percent of dry ingredients will ingeneral be suitable, with the preferred range being from 15 to 20 weightpercent.

Where the compositions are intended to be used as feeds, feedsupplements or feed pre-mixes, they will be mixed with suitableingredients of an animals nutrient ration. The solid orally ingestiblecarriers normally used for such purposes, such as distillers driedgrains, corn meal, fermentation residues, ground oyster shells, corn cobmeal, edible vegetable substances, soybean mill feed and soya grits areall suitable. The active compounds are intimately dispersed or admixedthroughout the solid inert carrier by methods such as grinding,stirring, milling or tumbling. By selecting proper diluents and byaltering the ratio of carrier to active ingredient, compositions of anydesired concentration may be prepared. Feed supplement formulationscontaining from about to 30% by weight of active ingredient areparticularly suitable for addition to feeds. The active compound isnormally dispersed or mixed uniformly in the diluent but in someinstances may be adsorbed on the carrier. These supplements are added tothe finished animal feed in an amount adequate to give the finalconcentration desired for controlling or treating the helminth infectionby way of the animal ration. Although the preferred level in feeds willdepend on the particular compound, 0.05 to 25% by weight of the activecompounds of this invention is normally included in the feed.

In addition to their use as anthelmintics, the compounds of formula Iare useful as fungicides, being particularly useful for the control ofplant pathogens, especially Botrytis cinerea which is the causativeorganism of grey mould in grapes.

Accordingly the present invention also provides a method of controllingfungi which attack plants which comprises applying to the locus of thefungus a fungicidal amount of at least one compound of formula I above.In carrying out the method of the present invention, the compound may beapplied to the foliage of crops and plants, and/or to the soil or waterin which the crops or plants are growing.

The fungicidal compounds of the present invention will normally be usedin the form of compositions comprising the active ingredient inassociation with a suitable diluent or carrier material such as one ormore of water,alcohols, glycols, glycol ethers, petroleum distillatesand various dispersion media such as surfactants,

emulsifiers and finely divided inert solids. The concentration of theactive ingredient in these compositions will vary depending on whetherthe composition is to be used directly as a dust or is intended as anemulsifiable concentrate or wettable powder designed to be subsequentlydiluted for example with water prior to use.

Since in use the compounds will normally be applied to infected orsusceptible plants in compositions containing from about 200 to 4,000ppm, preferably from about 400 to 2,000 ppm, of the active ingredient,it is normally convenient for ease of formulation, storage, package,etc., to formulate the active ingredient as a liquid or solidconcentrate composition.

Liquid concentrates may be prepared by dissolving, dispersing orsuspending from 0.1 to 10% of the active ingredient in water or asuitable water-miscible solvent such as, for example, suitable aromatic,aliphatic or cyclo-aliphatic hydrocarbons, ketones or alcohols to whichmay be added an emulsifying agent, for example a nonionic or ionic typeor blend such as condensation products of alkylene oxides with phenolsand organic acids, polyoxyethylene derivatives of sorbitan esters,complex ether-alcohols and the like.

Solid concentrate mixtures may be prepared by incorporating from S to30% of the active ingredient in a finely divided solid carrier such asbentonite, fullers earth, diatomaceous earth, hydrated silica,diatomaceous silica, kaolin, expanded mica, attapulgite, talc, chalk andthe like. Such concentrates may be formulated for direct use or may, ifdesired, be diluted with additional inert solid carriers to producedusting powders. Alternatively dispersing and/or wetting agents may beincorporated to form wettable powder concentrates which subsequently maybe dispersed in water or in other aqueous carriers to form spraycompositions. Suitable wetting and emulsifying agents include sodiumlauryl sulphate, sodium lignosulphate and other suitable nonionic andanionic surfactants or blends thereof.

The following Examples will further illustrate the preparation of thenovel compounds of this invention:

EXAMPLE 1 a. A solution of 6-ethoxycarbonyl-5-thiazolo-[3,2-

a]pyrimidinone (4.5 g.) and hydrazine hydrate (2 ml.) in ethanol (100ml.) was heated under reflux for 5 hours. White crystals formed whichwere filtered off and recrystallized from ethanol/dimethylformamide togive 7-ethoxycarbonyl-1H,4H- pyrimido[2,l-c]-[ l ,2,4]triazin-6-one,m.p. 275 C.

. By the method of (a) above but using6-ethoxycarbonyl-5-oxazolo-[3,2-a]pyrimidinone, 2 equivalents ofhydrazine and a reaction time of 0.5 hours, 7-ethoxycarbonyllH,4H-pyrimido[ 2, l -c l,2,4]triazin-6-one, m.p. 275 C., was obtained.

EXAMPLE 2 A solution of 6-ethoxycarbonyl-5-oxazolo[3,2-

a]pyrimidinone (1 g.) and hydrazine hydrate (2.5 ml.) in ethanol ml.)was heated under reflux for 18 hours. A solid formed which was filteredoff and recrystallized from dimethylformamide to givelH,4I-l-pyrimido[2,l-c]-[ l,2,4]triazin-6-one, 7- carboxylic acidhydrazide, m.p. 330 C. By the method of (a) above but using6-ethoxycarbonyl-5-thiazolo[3,2-a]-pyrimidinone, 6 equivalents ofhydrazine and a reaction time of 20 hours, lH,4H-pyrimido[2, l-c]-[ l,2,4]triazin-6- one, 7-carboxylic acid hydrazide, m.p. 330 C., wasobtained.

EXAMPLE 3 By the method of Example 1(a) above but using 2- methyl-6-ethoxycarbonyl-5-thiazolo[ 3 ,2-a] pyrimidinone (5 g.), hydrazine (1.5ml.) and a reaction time of 4.5 hours,3-methyl-7-ethoxycarbonylll-l,4H-pyrimido[2,l-c]-[l,2,4]-triazin-6-onewas prepared, m.p. 249 250 C., after recrystallization fromethanol/dimethylformamide.

EXAMPLE 4 By the method of Example 1(a) but using 2-phenyl-6-ethoxycarbonyl-5-thiazolo[3,2-a]pyrimidinone, 2 equivalents ofhydrazine and a reaction time of 10 hours,3-phenyl-7-ethoxycarbonyl-lH,4I-lpyrimido[2,l-c]-[ 1,2,41triazin-6-onewas prepared, m.p. 285 C., after recrystallization fromdimethylformamide.

'7 EXAMPLE By the method of Example 1(a) but using 7-methyl-5-thiazolo[3,2-a]-pyrimidinone, 25 equivalents of hydrazine and areaction time of 18 hours, 8-methylll-l,4H-pyrimido[ 2, l -c]-[l,2,4]triazin-6-one was prepared, m.p. 290 C., after recrystallizationfrom chloroform/dimethylsulphoxide.

EXAMPLE 6 By the method of Example 1(a) but using 3,7-dimethyl-5-thiazolo[3,2-a]-pyrimidinone, 5 equivalents of hydrazine anda reaction time of 125 hours, 4,8-dimethyl-lH,4H-pyrimido[2, l-c]-[1,2,4] triazin-6-one was obtained, m.p. 220 C., after recrystallizationfrom chloroform/petroleum ether.

EXAMPLE 7 A suspension of 7-ethoxycarbonyl-1H,4H-pyrimido[2,l-c]-[l,2,4]triazin-6-one (600 mg.) and silver oxide (500 g.)in a solution of methyl iodide (1 ml.) in dimethylformamide ml.) wasstirred at room temperature for 7 hours. The mixture was evaporated todryness and the solid extracted with chloroform. The chloroform extractswere evaporated to dryness and the residue recrystallized from ethanolto give l-methyl7-ethoxycarbonyl-lH,4H- pyrimido[2,l-c]-[ l,2,4]triazin-6-one, m.p. 173 C.

EXAMPLE 8 EXAMPLE 9 By the method of Example 7 but using 3-methyl-7-ethoxycarbonyl-1H,4H-pyrimido[2,l-c]-[ l ,2,4]triazin- 6-one, there wasprepared 1,3-dimethyl-7-ethoxycarbonyll H,4H-pyrimido[2, 1-c]-[l,2,4]triazin-6-one, m.p. 158 C., after recrystallization fromchloroform/carbon tetrachloride.

EXAMPLE 10 A solution of 2-methyl-6-ethoxycarbonyl-5-thiazolo[3,2-a1pyrimidinone (5 g.) and methyl hydrazine (20 ml.) inethanol (70 ml.) was heated under reflux conditions for hours. Thesolution was allowed to cool slightly and the solid which formed wasfiltered off, recrystallized twice from ethanol and once from water togive 1,3,N- trimethyll H,4H-pyrimido[2, l -c]-[ 1,2,4]-triazin- 6-one,7-carboxylic acid hydrazide, m.p. 196 C.

b. A solution of 1,3-dimethyl-7-ethoxycarbonyl-lH,4H-pyrimido[2,l-c]-[l,2,4]ttiazin-6-one (3.2 g.) and methylhydrazine(16 ml.) in ethanol (45 ml.) was refluxed for 14 hours. The solution wasallowed to cool and the resultant crystals filtered offi-Afterrecrystallization 3 times from ethanol and twice from water, there wasobtained, 1,3N- trimethyll H,4l-l-pyrimido[2, l-c]-[ l,2,4]triazin-6-one, 7-carboxylic acid hydrazide, m.p. 126 C. Microanalytical resultsobtained for each of the compounds of Examples 1 to 10 agreed with thetheoretical values to within i0.3%

We claim: 1. Compound of the formula:

wherein R represents hydrogen, C alkyl or CH Ar in which Ar representsphenyl optionally substituted by halogen, nitro, C alkyl or C alkoxy; Rrepresents hydrogen, C alkyl or the group Ar as defined above, the two Rgroups being the same or different; R is hydrogen or C alkyl; and Rrepresents hydrogen or COR in which R is C alkoxy, C alkylamino, orNHN(R) where R is as defined above and the two R groups may be the sameor difierent.

2. Compound as claimed in claim 1, wherein R represents hydrogen, Calkyl, benzyl, halobenzyl or nitrobenzyl; one of R is hydrogen and theother R is hydrogen, methyl, ethyl, phenyl, halophenyl or nitrophenyl; Ris hydrogen, methyl or ethyl; and R is hydrogen, methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, methylaminocarbonyl,dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl,hydrazinocarbonyl, methylhydrazinocarbonyl, dimethylhydrazinocarbonyl,ethylhydrazinocarbonyl, diethylhydrazinocarbonyl orbenzylhydrazinocarbonyl.

3. Compound as claimed in claim 1, wherein R and R are hydrogen, R isethoxycarbonyl and R is selected from C alkyl, benzyl or nitrobenzyl.

4. Compound as claimed in claim 1, wherein R and R are hydrogen, R ishydrazinocarbonyl or methylhydrazinocarbonyl, and R is selected fromhydrogen, C alkyl, benzyl or nitrobenzyl.

5. Compound as claimed in claim 3, wherein R is selected from methyl,s.butyl, benzyl or p.nitrobenzyl.

6. Compound as claimed in claim 1, wherein R and R are hydrogen, R ismethyl and R is hydrogen or 4- methyl.

7. Compound as claimed in claim 1, wherein R and R are hydrogen, R isethoxycarbonyl and R is 3- methyl or 3-phenyl.

8. Compound as claimed in claim 1, wherein R is methyl, R is 3-methyl, Ris hydrogen and R is ethoxycarbonyl or methylhydrazinocarbonyl.

9. Compound as claimed in claim 1, wherein R, R and R are hydrogen, andR is ethoxycarbonyl or hydrazinocarbonyl.

10. Compound as claimed in claim 1, wherein said compound is l-methylor1-benzyl-7-ethoxycarbonyl-l H,4H-pyrimido[2, l -c]-[l,2,4]triazin-6-one.

PC4050 UNITED STATES PATENT OFFICE (5/69) H h w I a a tmcA OF (IREGHNPatent No. 9 +l Dated September 26, 1972 Inventofls) David WilliamDunwell and Delme Evans It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

0n the frontpage after "Applnt No. 121,597" insert -Foreign ApplicationPriority Data March 11, 1970 Great Britain 157-'r/7o--.

In column 7, line 22, (500 g. should read --(5OO mg.

Signed and sealed this 18th day of December 1973.

(SEAL) Attest:

RENE D. TEGTMEYER Acting Commissioner of Patents EDWARD M.FLETCHER,JR.Attesting Officer

2. Compound as claimed in claim 1, wherein R1 represents hydrogen, C1-5alkyl, benzyl, halobenzyl or nitrobenzyl; one of R2 is hydrogen and theother R2 is hydrogen, methyl, ethyl, phenyl, halophenyl or nitrophenyl;R3 is hydrogen, methyl or ethyl; and R4 is hydrogen, methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, methylaminocarbonyl,dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl,hydrazinocarbonyl, methylhydrazinocarbonyl, dimethylhydrazinocarbonyl,ethylhydrazinocarbonyl, diethylhydrazinocarbonyl orbenzylhydrazinocarbonyl.
 3. Compound as claimed in claim 1, wherein R2and R3 are hydrogen, R4 is ethoxycarbonyl and R1 is selected from C1-5alkyl, benzyl or nitrobenzyl.
 4. Compound as claimed in claim 1, whereinR2 and R3 are hydrogen, R4 is hydrazinocarbonyl ormethylhydrazinocarbonyl, and R1 is selected from hydrogen, C1-5 alkyl,benzyl or nitrobenzyl.
 5. Compound as claimed in claim 3, wherein R1 isselected from methyl, s.butyl, benzyl or p.nitrobenzyl.
 6. Compound asclaimed in claim 1, wherein R1 and R4 are hydrogen, R3 is methyl and R2is hydrogen or 4-methyl.
 7. Compound as claimed in claim 1, wherein R1and R3 are hydrogen, R4 is ethoxycarbonyl and R2 is 3-methyl or3-phenyl.
 8. Compound as claimed in claim 1, wherein R1 is methyl, R2 is3-methyl, R3 is hydrogen and R4 is ethoxycarbonyl ormethylhydrazinocarbonyl.
 9. Compound as claimed in claim 1, wherein R1,R2 and R3 are hydrogen, anD R4 is ethoxycarbonyl or hydrazinocarbonyl.10. Compound as claimed in claim 1, wherein said compound is 1-methyl-or 1-benzyl-7-ethoxycarbonyl-1H,4H-pyrimido(2,1-c)-(1,2,4)triazin-6-one.